By Cheryl Guttman Krader Reviewed by Hilary Baldwin, MD
Acne vulgaris is the most common skin condition that dermatologists see, and thanks to the breadth of available therapeutic options, they have successfully treated patients with acne across the spectrum of disease severity.
Adding to this success, the FDA approval in the past 2 years (between August 2018 and August 2020) of 6 new products with indications for treating acne vulgaris is a key advance in patient care, considering that each product offers a distinct benefit, said Hilary Baldwin, MD.
The 6 new products include a novel oral antibiotic—sarecycline (Seysara, Almirall)—and 5 topical agents comprising 3 retinoids: trifarotene 0.005% cream (Aklief, Galderma), tretinoin 0.05% lotion (Altreno, Ortho Dermatologics), and tazarotene 0.045% lotion (Arazlo, Ortho Dermatologics); a topical tetracycline: minocycline 4.0% foam (Amzeeq, Foamix); and a first-in-class topical androgen receptor inhibitor: clascoterone 1.0% cream (Winlevi, Cassiopea) (Table).
“Our toolbox for treating patients with acne has not just gotten a lot bigger. It is a lot better,” said Dr. Baldwin, who is the Medical Director of the Acne Treatment and Research Center, Brooklyn, New York, and Clinical Associate Professor at Rutgers Robert Wood Johnson Medical Center, New Brunswick, New Jersey.
“These new products represent true innovations, including advanced formulations that can improve drug delivery, tolerability, and patient acceptance, as well as novel agents that can change the way we treat acne. With these options, I believe that the future is extremely bright for clinicians and our patients with acne.”
Clascoterone
Dr. Baldwin said that clascoterone 1.0% cream grants her wish for a topical acne medication that acts to inhibit sebum production. Moreover, it brings an alternative to isotretinoin for controlling sebum production in men.
“Our topical options for acne have allowed us to address 3 of the 4 factors that are involved in acne pathogenesis—hyperkeratinzation, inflammation, and inhibition of C. acnes. As a topical sebum inhibitor, clascoterone closes the tetrad so that we no longer have to prescribe an oral agent for patients who require sebum inhibition to have maximum control of their disease,” said Dr. Baldwin.
“If topical clascoterone works as well in the real world as it did in the clinical trials, it will certainly be an important option.”
Topical retinoids
Trifarotene 0.005% cream is a novel topical retinoid with data on its efficacy for treating truncal acne. Dr. Baldwin explained that trifarotene is the first retinoid that has high selectivity for the γ subtype of the retinoic acid receptor (RAR). Adapalene, tazarotene, and tretinoin all bind to both RAR subtypes found in the skin, RARγ and RARβ. RARγ is the more prevalent.
“It is not clear that there is a clinical benefit of the selectivity of trifarotene for RARγ in terms of improving efficacy or reducing side effects relative to other retinoid molecules. It may explain, however, why trifarotene could be formulated topically in such a low concentration, just 0.005%,” she said.
“This may translate into less systemic retinoid exposure, and that could have relevance in women who might get pregnant while using the medication as well as patients utilizing it on face, chest, and back.”
Discussing truncal acne, Dr. Baldwin commented, “We have always assumed that acne is acne and that lesions would respond similarly to treatment no matter the anatomic location. However, we have been lacking confirmatory evidence. The design of the phase 3 trials for trifarotene addressed that gap by analyzing lesion counts on the shoulders, upper back and anterior chest as well as the face.”
With their novel formulations, both tretinoin 0.05% lotion and tazarotene 0.045% address the tolerability issue that historically plagues topical retinoid treatment. Approved in August 2018, tretinoin 0.05% lotion became the first available topical retinoid formulated in a lotion vehicle.
Both formulations utilize a unique polymeric emulsion technology engineered to deliver the active ingredient and moisturizing agents evenly on the skin. The tazarotene formulation consists of a 3-dimensional mesh matrix that holds water and water-soluble hydrating agents along with droplets of tazarotene and oil-soluble moisturizing agents. The mesh dissolves upon contact with salts that are present on the skin surface, releasing the tretinoin or tazarotene and moisturizing/hydrating ingredients uniformly.
“In clinical use, the end result of the novel formulation is that the irritation profile of topical tretinoin or tazarotene is dramatically reduced. It is not known which of the formulation’s features—the inclusion of moisturizing ingredients, the micronization of the active ingredient, or the polymeric technology that prevents larger ‘clumps’ of irritating tazarotene coming in contact with the skin—is most important for contributing to this benefit,” Dr. Baldwin said.
“Speaking from personal experience, however, I was able to use tazarotene 0.045% lotion on my skin for 7 consecutive days without having to take a break. That was never possible when I tried using any of the previously available tazarotene products because they were so drying.”
New tetracycline treatments
Minocycline 4.0% foam brings a topical acne treatment in a patient-preferred vehicle and overcomes issues accompanying existing antibiotic options.
“Minocycline foam fills an important gap in our antibiotic therapies. As a topical product it minimizes concerns about systemic side effects, and unlike topical benzoyl peroxide, it does not bleach fabric,” Dr. Baldwin said.
She also pointed out that pharmacokinetics data for minocycline foam show that its use results in very low or no systemic exposure to minocycline despite achieving very high levels in the skin.
“The cutaneous levels of minocycline are so high that we may not have to worry about the development of C. acnes resistance and therefore would not have to use benzoyl peroxide in combination to limit the emergence of resistance. Simplifying the treatment regimen by reducing the number of medications a patient needs to use has advantages for convenience, cost, and compliance,” Dr. Baldwin said.
Sarecycline is a new tetracycline-derived antibiotic with several distinguishing features, including approval for use in patients as young as 9 years of age, narrower antimicrobial spectrum, and lower propensity to induce bacterial resistance.
“Sarecycline has minimal activity against gram-negative enteric bacteria. Theoretically therefore it is less likely than doxycycline or minocycline to alter the gastrointestinal (GI) tract flora, and in fact it had very good GI tolerability in the clinical trials,” Dr. Baldwin said.
“In vitro testing also shows that sarecycline has a low potential for inducing C. acnes resistance as it had a spontaneous mutation frequency on the order of 10-10. The clinical relevance of these laboratory data, however, remains to be seen.”
Dr. Baldwin also noted that the sarecycline pivotal trials captured changes in lesion counts for back and chest acne.
“With these data, we now have good evidence documenting that 2 of our therapeutic options for acne work well for truncal acne,” she said.
Implementing the new options
Dr. Baldwin said that although she was satisfied with her ability to effectively treat acne prior to the spate of FDA approvals (assuming patients had access to brand-name medications), she promptly adopted the new options as they became available.
“I strongly believe in embracing new technologies and new therapies that represent improvements in our clinical options. I see no reason to reserve them for situations involving patients who are not responding to older agents,” she said.
“If I were the patient, I would not want to be treated with medications that may be less effective or that could irritate my skin if better alternatives are available.”
Disclosures
Dr. Baldwin has ties with Almirall, Cassiopeia, Foamix, Galderma, and Ortho Dermatologics.
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